Question

In this chapter, we focused on cancer as a genetic disease. In particular, we discussed the relationship between cancer, the cell cycle, and mutations in proto-oncogenes and tumor-suppressor genes. Based on your knowledge of these topics, answer several fundamental questions: (a) How do we know that malignant tumors arise from a single cell that contains mutations? (b) How do we know that cancer development requires more than one mutation? (c) How do we know that cancer cells contain defects in DNA repair?

Short answer

Question: Explain the genetic basis of cancer, including the origin of malignant tumors, the requirement of multiple mutations, and the presence of defects in DNA repair. Answer: The genetic basis of cancer involves the accumulation of mutations in key genes, leading to uncontrolled cell growth and division. Malignant tumors originate from a single mutated cell that undergoes clonal expansion, forming a population of cells with the same genetic alterations. Cancer development requires more than one mutation, as supported by the multiple-hit hypothesis, which proposes that successive mutations lead to progressively severe cellular abnormalities. Defects in DNA repair mechanisms are also common in cancer cells, resulting in a higher rate of mutations and further contributing to the development of cancer.

Step-by-step solution

a) How do we know that malignant tumors arise from a single cell that contains mutations?

To answer this question, we need to understand the concept of clonal expansion. When a single mutated cell divides uncontrollably and accumulates additional mutations, it forms a population of cells with the same genetic alterations, called a clone. The malignant tumor that arises from this process is derived from these clones. Evidence supporting the idea that tumors arise from a single mutated cell includes: - Tumors usually display genetic homogeneity, meaning that their cells have similar mutations and genetic markers. - Experiments have shown that injecting a single cancerous cell into an organism can cause the formation of a tumor. - The process of tumorigenesis is a stepwise process, with the accumulation of mutations driving the progression from a benign tumor to a malignant one.

b) How do we know that cancer development requires more than one mutation?

The development of cancer is a complex, multi-step process. It has been observed that not all cells with certain mutations progress to cancer, indicating that multiple mutations are required for full malignant transformation. Additionally, the process of tumorigenesis shows a general pattern in which successive mutations lead to increasingly severe cellular abnormalities. This concept is known as the multiple-hit hypothesis in cancer development. Evidence for the requirement of more than one mutation in cancer development includes: - The fact that cancer incidence rates increase with age, which correlates with the time required for the accumulation of multiple mutations. - Observations of multistage carcinogenesis in experimental models, such as the conversion of normal cells to malignant ones with sequential genetic alterations. - Identification of proto-oncogenes and tumor-suppressor genes, both of which can contribute to cancer development when mutated, and their mutations are usually found together in cancer cells.

c) How do we know that cancer cells contain defects in DNA repair?

Cancer cells often have a higher rate of mutations than normal cells, which can be attributed to defects in their DNA repair mechanisms. DNA repair is crucial for maintaining the integrity of genetic material when it gets damaged. Many studies have shown that defects in DNA repair pathways contribute to the accumulation of genetic changes in cancer cells. Evidence for defects in DNA repair in cancer cells includes: - Mutations in genes responsible for DNA repair are often found in cancer cells, suggesting that these defects play a role in tumorigenesis. - People with inherited deficiencies in DNA repair genes have higher cancer risks than those without these deficiencies. - DNA repair deficient cells have been shown to become cancerous more easily when exposed to carcinogens that induce DNA damage. In conclusion, understanding the genetic basis of cancer helps us to answer fundamental questions about its development, such as the origin of malignant tumors, the requirement of multiple mutations, and the presence of defects in DNA repair.